Methods for crimping a polymeric stent onto a delivery balloon

ABSTRACT

A medical device-includes a polymer stent crimped to a catheter having an expansion balloon. The stent is crimped to the balloon by a process that includes heating the stent to a temperature below the polymer&#39;s glass transition temperature to improve stent retention without adversely affecting the mechanical characteristics of the stent when later deployed to support a body lumen.

BACKGROUND OF THE INVENTION

This application claims prority under 35 U.S.C. §120 as a continuationapplication of U.S. application Ser. No. 12/772,116 filed Apr. 30, 2010now U.S. Pat. No. 8,261,432 B 2.

Field of the Invention

The present invention relates to drug-eluting medical devices; moreparticularly, this invention relates to processes for crimping apolymeric stent to a delivery balloon.

Background of the Invention

The art recognizes a variety of factors that affect a polymeric stent'sability to retain its structural integrity when subjected to externalloadings, such as crimping and balloon expansion forces. Theseinteractions are complex and the mechanisms of action not fullyunderstood. According to the art, characteristics differentiating apolymeric, bio-absorbable stent scaffolding of the type expanded to adeployed state by plastic deformation from a similarly functioning metalstent are many and significant. Indeed, several of the accepted analyticor empirical methods/models used to predict the behavior of metallicstents tend to be unreliable, if not inappropriate, as methods/modelsfor reliably and consistently predicting the highly non-linear behaviorof a polymeric load-bearing, or scaffolding portion of aballoon-expandable stent. The models are not generally capable ofproviding an acceptable degree of certainty required for purposes ofimplanting the stent within a body, or predicting/anticipating theempirical data.

Moreover, it is recognized that the state of the art in medicaldevice-related balloon fabrication, e.g., non-compliant balloons forstent deployment and/or angioplasty, provide only limited informationabout how a polymeric material might behave when used to support a lumenwithin a living being via plastic deformation of a network of ringsinterconnected by struts. In short, methods devised to improvemechanical features of an inflated, thin-walled balloon structure, mostanalogous to mechanical properties of a pre-loaded membrane when theballoon is inflated and supporting a lumen, simply provides little, ifany insight into the behavior of a deployed polymeric stent scaffolding.One difference, for example, is the propensity for fracture or cracks todevelop in a stent scaffolding. The art recognizes the mechanicalproblem as too different to provide helpful insights, therefore, despitea shared similarity in class of material. At best, the balloonfabrication art provides only general guidance for one seeking toimprove characteristics of a balloon-expanded, bio-absorbable polymericstent.

Polymer material considered for use as a polymeric stent scaffolding,e.g. PLLA or PLGA, may be described, through comparison with a metallicmaterial used to form a stent scaffolding, in some of the followingways. A suitable polymer has a low strength to weight ratio, which meansmore material is needed to provide an equivalent mechanical property tothat of a metal. Therefore, struts must be made thicker and wider tohave the strength needed. The scaffolding also tends to be brittle orhave limited fracture toughness. The anisotropic and rate-dependantinelastic properties (i.e., strength/stiffness of the material variesdepending upon the rate at which the material is deformed) inherent inthe material only compound this complexity in working with a polymer,particularly, bio-absorbable polymer such as PLLA or PLGA.

Processing steps performed on, design changes made to a metal stent thathave not typically raised concerns for, or require careful attention tounanticipated changes in the average mechanical properties of thematerial, therefore, may not also apply to a polymer stent due to thenon-linear and sometimes unpredictable nature of the mechanicalproperties of the polymer under a similar loading condition. It issometimes the case that one needs to undertake extensive validationbefore it even becomes possible to predict more generally whether aparticular condition is due to one factor or another—e.g., was a defectthe result of one or more steps of a fabrication process, or one or moresteps in a process that takes place after stent fabrication, e.g.,crimping. As a consequence, a change to a fabrication process,post-fabrication process or even relatively minor changes to a stentpattern design must, generally speaking, be investigated more thoroughlythan if a metallic material were used instead of the polymer. Itfollows, therefore, that when choosing among different polymeric stentdesigns for improvement thereof, there are far less inferences,theories, or systematic methods of discovery available, as a tool forsteering one clear of unproductive paths, and towards more productivepaths for improvement, than when making changes in a metal stent.

It is recognized, therefore, that, whereas inferences previouslyaccepted in the art for stent validation or feasibility when anisotropic and ductile metallic material was used, such inferences wouldbe inappropriate for a polymeric stent. A change in a polymeric stentpattern may affect, not only the stiffness or lumen coverage of thestent in its deployed state supporting a lumen, but also the propensityfor fractures to develop when the stent is crimped or being deployed.This means that, in comparison to a metallic stent, there is generallyno assumption that can be made as to whether a changed stent pattern maynot produce an adverse outcome, or require a significant change in aprocessing step (e.g., tube forming, laser cutting, crimping, etc.).Simply put, the highly favorable, inherent properties of a metal(generally invariant stress/strain properties with respect to the rateof deformation or the direction of loading, and the material's ductilenature), which simplify the stent fabrication process, allow forinferences to be more easily drawn between a changed stent patternand/or a processing step and the ability for the stent to be reliablymanufactured with the new pattern and without defects when implantedwithin a living being.

A change in the pattern of the struts and rings of a polymeric stentscaffolding that is plastically deformed, both when crimped to, and whenlater deployed by a balloon, unfortunately, is not as easy to predict asa metal stent. Indeed, it is recognized that unexpected problems mayarise in polymer stent fabrication steps as a result of a changedpattern that would not have necessitated any changes if the pattern wasinstead formed from a metal tube. In contrast to changes in a metallicstent pattern, a change in polymer stent pattern may necessitate othermodifications in fabrication steps or post-fabrication processing, suchas crimping and sterilization.

One problem frequently encountered with a stent for delivery to a sitein a body using a balloon is reliably retaining the stent on the balloonas it passes through tortuous anatomy. If the stent is not held on theballoon with sufficient force, it can slip off of the balloon duringtransit to the target site. For a metallic stent, there are severalapproaches proposed for increasing the retention of a stent to a balloonduring transit to the target site. However, methods proposed thus farfor retaining the polymer stent on a balloon are in need of improvement.

In light of the foregoing problems, there is a need for improving theretention of a polymer stent on a balloon while avoiding adverse effectson the mechanical characteristics of the load bearing, polymerscaffolding when the scaffolding is fully deployed to support a lumen.

SUMMARY OF THE INVENTION

It has been determined that more precise control of a crimpingtemperature aids in retention of a polymer stent on a balloon. A balloonexpandable polymer stent made of a bio-absorbable material shouldbenefit from processes disclosed herein. Polymers such as PLLA and PLGAhave a semi-crystalline structure. Control of temperature within aspecific range for these materials, in relation to their glasstransition temperature (Tg), can improve the retention force on aballoon without causing adverse effects on the polymer stent's strengthand stiffness properties when it is later expanded by the balloon.

It is known that for a polymeric stent the glass transition temperature(Tg) of its matrix material has to be higher than physiologicaltemperature (37° C.) in order to maintain enough radial strength afterits implantation. PLLA material has a Tg at around 55-60° C. When a PLLAstent is crimped at room temperature, free polymer chain movement canhardly happen. It is therefore difficult to crimp a stent from arelatively large starting diameter to a designated final crimpingdiameter at, or below physiological conditions. One way proposed tosolve the problem is to crimp a stent with a higher crimping force. Thissolution, however, will likely lead to more cracks when the stent isdeployed, or when it is crimped. Crimping more slowly can reduce thenumber of cracks. However, deformation must be performed at a rate tooslow for practical use in stent production.

The invention provides a medical device including a polymer stentcrimped to a balloon. The invention also provides a process for crimpinga polymer stent to a balloon. The polymer stent is expanded forplacement within a lumen of the body by plastic deformation of thepolymer scaffolding of the stent. The crimping process used to place thestent on the balloon includes heating the stent to a temperature thatenables the polymer in the stent's scaffolding to deform to a reduced,crimping diameter without causing detrimental effects to the mechanicalproperties of the polymer material when it is later deployed within alumen. The process increases the retention force, or resistance todislodgment from the balloon when the medical device is deliveredthrough tortuous anatomy.

In one embodiment, a heated crimper is used to reduce the diameter ofthe stent from the cut diameter to the final profile. Heat is used toraise the temperature of the stent allowing it to be deformed withoutdamage and to retain the final shape. The temperature at which theprocess is run is, in the preferred embodiments, within a narrow rangeto achieve a desired outcome. For a stent made from PLLA material, itwas found that the retention of the stent on the balloon was less thandesired when it was crimped near room temperature. On the other hand,when the stent was crimped at higher temperatures (55° C. and above), itdeveloped more cracks upon deployment, which affects the deployedstrength of the stent.

In accordance with the foregoing objectives, there is provided a methodfor crimping a polymer stent to a balloon and an apparatus including astent crimped to a catheter having a delivery balloon.

In one aspect of the invention there is a method for crimping aballoon-expanded stent scaffolding to a balloon, comprising the stepsof: providing a tube comprising PLLA characterized by a glass transitiontemperature range having a lower limit of about 55° C.; radially orbi-axially expanding the tube to increase its radial strength; formingthe scaffolding from the radially or bi-axially expanded tube, includingthe steps of forming; and crimping the scaffolding to the balloon whilethe scaffolding has a temperature of between, or between about 48° C.and 54° C. In other embodiments, the temperature range is, or about48-50 degrees centigrade, or the temperature is, or about 48° C.

In another aspect of the invention, a method for crimping aballoon-expanded stent scaffolding to a balloon includes the steps ofproviding a tube comprising a polymer characterized by a glasstransition temperature range having a lower limit of Tg-low; radiallyexpanding the tube to increase its radial strength; forming thescaffolding from the radially-expanded tube; and crimping thescaffolding to the balloon while the scaffolding has a temperature ofbetween about Tg-low and 15 degrees below Tg-low. The polymer may bePLLA or PLGA. The temperature range may be between about Tg-low and 10degrees below Tg-low. The temperature range may be between about Tg-lowand 5 degrees below Tg-low. The scaffold may have a circumferentialseries of closed cells having a W-shape and linear link strutsconnecting the W-shape cells. The balloon may be a PEBAX balloon. Thecrimping may reduce the scaffold size from a first diameter to a seconddiameter that is at least 2.5 times smaller than the tube diameter.

In another aspect of the invention, a medical device includes a polymerscaffolding crimped to a balloon; wherein the polymer scaffolding isretained to the balloon with a retention force of at least about 1.0lbs.; wherein the polymer scaffolding is capable of being plasticallyexpanded within a body lumen by the balloon and providing a therapeuticbenefit to the body lumen including radially supporting the lumen, theplastically expanded polymer scaffolding having an outer diameter of atleast about 2.5 times the outer diameter of the polymer scaffoldingcrimped to the balloon; and wherein after the polymer scaffolding hasbeen plastically expanded the polymer scaffolding has a network ofstruts connecting ring elements, wherein the scaffolding includescircumferential series of closed cells having a W-shape and a linearlink strut connecting the W-shape cells.

In another aspect of the invention, a medical device includes a polymerscaffolding crimped to a balloon; wherein the polymer scaffolding isretained to the balloon with a retention force of at least about 1.0lbs.; wherein the polymer scaffolding is capable of being plasticallyexpanded within a body lumen by the balloon and providing a therapeuticbenefit to the body lumen including radially supporting the lumen, theplastically expanded polymer scaffolding having an outer diameter of atleast about 2.5 times the outer diameter of the polymer scaffoldingcrimped to the balloon; wherein after the polymer scaffolding has beenplastically expanded the polymer scaffolding has a network of strutsconnecting ring elements; and wherein the scaffolding includes ringstructures forming a tubular body having a distal end, a proximal end,and an intermediate segment between the distal and proximal ends, thering structures connected to each other by linear link struts that areoriented axially, the ring structures and link struts forming W-shapeclosed cells.

The scope of the methods and apparatus of the invention also encompassprocesses that crimp a scaffold as substantially described in US Pub.No. 2010/0004735 and US Pub. No. 2008/0275537. The thickness of the tubefrom which the scaffold is formed may have a thickness of between 0.10mm and 0.18 mm, and more narrowly at or about 0.152 mm. The scaffold maybe made from PLLA. And the scaffold may be crimped to a PEBAX balloon.

Incorporation By Reference

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference, and as if eachsaid individual publication or patent application was fully set forth,including any figures, herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a process for fabricating a scaffolding of a polymer stentand crimping the fabricated stent to a balloon according to theinvention.

FIG. 2 is planar view of a portion of a polymer stent scaffolding thatwas crimped to a balloon according to aspects of the invention. Thisview describes the stent pattern of the load-bearing structure of thescaffolding of the fully deployed stent that is crimped to a balloonaccording to the process of FIG. 1.

DETAILED DESCRIPTION OF EMBODIMENTS

The “glass transition temperature,” Tg, is the temperature at which theamorphous domains of a polymer generally change from a brittle, vitreousstate to a solid deformable or ductile state at atmospheric pressure. Inother words, the Tg corresponds to the temperature where the onset ofnoticeable segmental motion in the chains of the polymer occurs. When anamorphous or semi-crystalline polymer is exposed to an increasingtemperature, the coefficient of expansion and the heat capacity of thepolymer both increase as the temperature is raised, indicating increasedmolecular motion. As the temperature is raised the actual molecularvolume in the sample remains constant, and so a higher coefficient ofexpansion points to an increase in free volume associated with thesystem and therefore increased freedom for the molecules to move. Theincreasing heat capacity corresponds to an increase in heat dissipationthrough movement. Tg of a given polymer can be dependent on the heatingrate and can be influenced by the thermal history of the polymer.Furthermore, the chemical structure of the polymer heavily influencesthe glass transition by affecting mobility.

Poly(lactide-co-glycolide) (PLGA) and Poly (L-lactide) (PLLA) areexamples of a class of semi-crystalline polymers that may be used toform the scaffolding for the stent structures described herein. PLLA isa homopolymer and PLGA is a co-polymer. The percentage of glycolide (GA)in a scaffold constructed of PLGA may vary, which can influence thelower range of Tg. For example, the percentage of GA in the matrixmaterial may vary between 0-15%. For PLLA, the onset of glass transitionoccurs at about 55 degrees Celsius. With an increase of GA from about 0%to 15% the lower range for Tg for PLGA can be correspondingly lower byabout 5 degrees Celsius.

In one embodiment, a tube is formed by an extrusion of PLLA. The tubeforming process described in US Pub. No. 2010/00025894 may be used toform this tube. The finished, solidified polymeric tube of PLLA may thenbe deformed in radial and axial directions by a blow molding processwherein deformation occurs progressively at a predetermined longitudinalspeed along the longitudinal axis of the tube. For example, blow moldingcan be performed as described in U.S. Publication No. 2009/0001633. Thisbiaxial deformation, after the tube is formed, can produce noticeableimprovement in the mechanical properties of the stent structural memberscut from the tube without this expansion. The degree of radial expansionthat the polymer tube undergoes characterizes the degree of inducedcircumferential molecular or crystal orientation. In a preferredembodiment, the radial expansion ratio or RE ratio is about 450% of thestarting tube's inner diameter and the axial expansion ratio or AE ratiois about 150% of the starting tube's length. The ratios RA and AE aredefined in US Pub. No. 2010/00025894.

The above scaffolding's outer diameter may be designated by where it isexpected to be used, e.g., a specific location or area in the body. Theouter diameter, however, is usually only an approximation of what willbe needed during the procedure. For instance, there may be extensivecalcification that breaks down once a therapeutic agent takes effect,which can cause the stent to dislodge in the vessel. Further, since avessel wall cannot be assumed as circular in cross-section, and itsactual size only an approximation, a physician can choose to over-extendthe stent to ensure it stays in place. For this reason, it is preferredto use a tube with a diameter larger than the expected deployed diameterof the stent.

In one embodiment the ratio of deployed to fully crimped diameter isabout 2.5. In this embodiment, the crimped diameter corresponds to anouter diameter that is only about 40% of the starting diameter. Hence,when deployed the drug eluting stent is expected to increase in size upto about 2.5 times its stowed or crimped diameter size.

In one particular example, a stent is formed from a biaxially expandedtube having an outer diameter of 3.5 mm, which approximately correspondsto a deployed diameter (the stent may be safely expanded up to 4.0 mmwithin a lumen). When crimped on the balloon, the stent has an outerdiameter of 1.3 mm, or about 37% of the starting tube diameter of 3.5mm.

As discussed earlier, fabrication of a balloon-expanded polymer stentpresents challenges that are not present in metallic stents. Onechallenge, in particular, is the fabrication of a polymer scaffolding,which means the load bearing network of struts including connectorslinking ring elements or members that provide the radial strength andstiffness needed to support a lumen. In particular, there exists ongoingchallenges in fabricating a polymer scaffolding (hereinafter“scaffolding”) that is capable of undergoing a significant degree ofplastic deformation without loss of strength, e.g., cracks or fractureof struts. In the disclosed embodiments, a polymer scaffolding iscapable of being deformed from a crimped diameter to at least 2.5 timesthe crimped diameter without significant loss of strength. Moreover, thepolymer scaffolding is retained on a delivery balloon with a retentionforce that is significantly higher than previous methods of stentretention for a polymer stent.

The invention addresses the unique challenges presented by a polymerstent that needs to be retained on a balloon. These challenges arepresent for several reasons. First, there is less space availablebetween struts in a crimped state, which prevents balloon material fromextending between struts. As a result, there is less abutment orinterference between struts and balloon material, whichinterference/abutment has previously been relied upon to increase theretention force of the stent on a balloon. This condition is a result ofthe need to fabricate wider and thicker struts for the polymer stent, ascompared to a metal stent, so as to provide adequate, deployed radialstrength. Second, a polymer, unlike a metal, is far more sensitive tochanges in temperature. The art has previously relied on heat to retaina metal stent on a balloon. However, the temperatures that havepreviously been found effective for stent retention fall within a Tg ofthe polymer. Such temperature ranges have, therefore, been avoided sinceheating of a polymer scaffolding to within, or above Tg inducessignificant changes in the molecular orientation of the polymer materialthat result in loss of strength when the scaffolding is plasticallydeformed to its deployed diameter.

The art has previously devised methods for retaining a polymer stent ona delivery balloon in response to these challenges. In one example, thestent is crimped to the delivery balloon at a temperature well below thepolymer's Tg. Then the stent, disposed between ends of the balloon, isthermally insulated from the balloon's ends. The ends of the balloon arethen heated to about 185 degrees Fahrenheit to expand the diameter ofthe balloon material at its ends. The expanded balloon ends form raisededges abutting the stent ends to resist dislodgment of the stent fromthe balloon. In one example, this process provided a retention force ofabout 0.35 lb. for a Poly (L-lactide) (PLLA) scaffolding crimped to apolymide-polyether block co-polymer (PEBAX) balloon.

As explained more fully below, it was found, unexpectedly, that there isa certain degree of beneficial movement between interconnected polymerchains of a stent structure heated to temperatures just below Tg of thepolymer when the stent is being crimped to a balloon, versus the samestent crimped to the balloon at a lower temperature, such as roomtemperature. For example, for a controlled temperature of between about48 and 54 degrees, 48-50 degrees or 48 degrees Celsius it was found thata PLLA stent crimped to a balloon exhibited noticeable improvement inthe retention force of the stent on the balloon, while not concomitantlyproducing unacceptable side effects for the deployed stent, e.g.,excessive cracking or void formation, fracture or loss of memory in thematerial affecting its deployed radial stiffness qualities.

One problem encountered with fabrication of a stent for delivery to asite in a body using a balloon is the ability of the stent to be safelycrimped to the balloon so that an adequate retention force isestablished between the stent and balloon. A “retention force” for astent crimped to a balloon means the maximum force, applied to the stentalong the direction of travel through a vessel, that the stent-balloonis able to resist before dislodging the stent from the balloon. Theretention force for a stent on a balloon is set by a crimping process,whereby the stent is plastically deformed onto the balloon surface toform a fit that resist dislodgment of the stent from the stent. Factorsaffecting the retention of a stent on a balloon are many. They includethe extent of surface-to-surface contact between the balloon and stent,the coefficient of friction of the balloon and stent surfaces, and thedegree of protrusion or extension of balloon material between struts ofthe stent. For a metal stent there are a wide variety of methods knownfor improving the retention force of a stent on a balloon viamodification of one or more of the foregoing properties; however, manyare not suitable or of limited usefulness for a polymeric stent, due todifferences in mechanical characteristics of a polymer stent verses ametal stent as discussed earlier. Most notable among these differencesis brittleness of the polymer material suitable for balloon-expandedstent fabrication, verses that of a metal stent. Whereas a metal stentmay be deformed sufficiently to obtain a desired retention force, therange of deformation available to a polymer stent, while avoidingcracking or fracture-related problems, by comparison, is quite limited.

For polymeric stents, the glass transition temperature (Tg) of itsmatrix material has to be higher than physiological temperatures (37degrees Celsius) in order to maintain radial strength afterimplantation. A stent formed from PLLA has a Tg of about 55-60 degreesCelsius. When a PLLA stent is crimped to a balloon at around 25 degreesCelsius, a free polymer chain movement hardly occurs. As a consequence,the PLLA is brittle and susceptible to crack formation. Moreover, atthis temperature, well below Tg, the stent will tend to recoil or reverttowards its starting diameter of the tube, to a certain degree, due tothe memory in the material. In addition, when the stent is deformedduring crimping, the induced strain in the polymer matrix will cause thestent to enlarge to a certain degree once the crimping force is removed,since there will be some percentage of elastic deformation when thestent is crimped to the balloon, which causes the stent to reverttowards its original diameter when the crimping force is relieved. Thisdegree of elastic recoil, so to speak, limits the amount of retention ofthe stent on the balloon since the degree of contact between stent andballoon is reduced. Stated somewhat differently, when there is elasticrecoil to a larger diameter, the normal force the stent imparts on theballoon while the crimping force is applied, which is proportional tomagnitude of the retention force, decreases once the crimper is removeddue to the percentage of elastic recoil in the stent.

One solution is to increase the retention force beyond that of the finalcrimped diameter. However, when crimping to a diameter of about 2.5times less than a starting diameter to increase the retention force,consideration must given to increased instances of crack formation inthe stent. These cracks can render the stent incapable of functioningproperly when fully deployed by the balloon. There can be significantloss in radial stiffness and strength resulting in fracture. As aconsequence, crack or loss of strength avoidance is an ongoing concernwhen efforts are made to a crimp polymer stent sufficiently from astaring diameter, preferably near the deployed diameter, to a designatedfinal, crimping diameter to increase the retention force.

A polymer material's resistance to fracture, particularly when deformedat temperatures well below Tg, is dependent upon the rate at which thematerial is deformed. However, the inventors found that a solution tothe stent retention/cracking problem described above is not found bysimply decreasing the rate at which the stent is crimped onto theballoon. The rates that would produce noticeable improvements in stentretention without loss of strength would be infeasible for stentproduction.

In finding a solution to the stent retention problem, it was initiallyunclear whether stent retention, without detrimental damage being doneto the stent, might be improved by increasing or varying balloonpressure during crimping, initiating stages of stent crimping includingdifferent rates, interim and final hold times at various crimperdiameters, e.g., pre-crimping steps, or increasing the temperature ofthe stent while it was being crimped, or a combination of these factors.A preliminary study was conducted to determine whether modification ofone or more of these factors in a polymer scaffold crimping processmight improve stent retention. Thus, factors including temperature, holdtime, balloon pressure force, pressure sequence, pressure initiationsize, and speed of crimping were initially studied. Results were studiedunder a multi-factored statistical approach to identify the key factorsaltering scaffold retention to a balloon. For this preliminary study, aniris crimper was used to crimp the stent. The scaffold was heated byheating the crimper jaws, although the scaffold may alternatively beheated by a forced hot air gas or heated fluid for expanding theballoon.

Based on this multi-factored study it was hypothesized that a carefullychosen temperature range might improve results, which came as asurprise. It was previously believed there would be little, or nobenefit to heating a scaffold during crimping because either a raisedtemperature would induce molecular motion destroying the chain alignmentneeded to give the scaffold its deployed strength properties, or thetemperature was too low to affect either the scaffold or the balloon.

A more narrow-focused study was conducted to identify a temperaturerange that might produce a significant difference in scaffold retentionforce without causing adverse effects on the deployed or crimpedscaffold. TABLES 1 and 2, below, provide statistics for a retentionforce of a polymer scaffold-balloon as a function of the scaffoldtemperature during crimping. The crimping process was similar to thatdescribed in FIG. 1. Two studies were conducted, one for scaffoldtemperatures of 37-48° C. and the other for scaffold temperatures of48-80° C., respectively. Both tests evaluated the retention force for aPLLA scaffolding having the pattern described in U.S. 2010/0004735 andcrimped to a PEBAX balloon. More specifically, a first study includedconducting several trials at each of 37° C., 42.5° C. and 48° C. and asecond study included conducting several trials at each of 48° C., 55°C., 65° C. and 80° C.

TABLES 1 and 2 show the mean and standard deviation in retention force(obtained using a standard pull-off test procedure) for a PLLAscaffolding having the pattern described in U.S. 2010/0004735 andcrimped to a PEBAX balloon. “Number” refers to the number of trials runat the corresponding scaffold temperatures.

TABLE 1 Temp (Celsius) Number Mean Std Dev 48 11 1.18 0.33 55 9 1.160.15 65 8 1.41 0.17 80 4 2.03 0.20

TABLE 2 Temp (Celsius) Number Mean Std Dev 37 20 0.74 0.19 42.5 21 1.240.11 48 13 1.24 0.14

Modifying the pressure and hold time of the scaffolding on the stent forcrimping temperatures of 40° and 55° C. improved the scaffold retention.However, modifying these parameters outside of this range produce littlechange. Specifically, for a 40° and 55° C. range of crimping theretention may be improved by balloon pressure being increased to raisethe balloon diameter to the pre-crimp stent diameter, then the stent wascrimped on the balloon to a final crimp diameter while pressure isreleased. Additionally, the stent may be crimped down to an intermediatediameter, then the balloon is deflated then re-inflated, followed bycrimping the stent down to a final crimp diameter.

FIG. 1 is a process diagram illustrating the steps used to fabricate apolymer scaffold and crimp the scaffold to a balloon. In this example, ascaffold was formed from a radially expanded tube of PLLA. The scaffoldhad a strut pattern as shown in FIG. 2. The struts had a thickness ofabout 0.152 mm and the balloon used was a PEBAX balloon. An iris crimperwas used to crimp the scaffold to the balloon.

A crimping process may proceed as follows. In preparation for thecrimping operation, the crimp head diameter is moved to an intermediateposition that is larger than the scaffold starting outer diameter (OD).The temperature of the jaws is raised to, or to about 48° C. and isallowed to stabilize at that temperature. A delivery catheter (holdingthe balloon) is chosen with the correct size to fit the scaffold.

The scaffold is placed onto the balloon catheter with the distal portionof the scaffold aligned with the distal portion of the catheter. Thecatheter is then placed onto a sliding alignment carriage. A finaladjustment is made to the scaffold to position it between balloonmarkers on the catheter. The scaffold and catheter is moved into thecrimp jaws, by sliding the carrier forward.

The cycle is initiated by the operator. As an example, for a 3.0×18 mmscaffold, the ID of the crimp head moves to a diameter of 0.083″ whereit remains for 30 seconds. This is stage 1. The system movesautomatically to stage 2 where the head moves to an ID of 0.068″ and isheld for 15 seconds. During this stage, the balloon catheter is inflatedto 17 psi. After this stage is complete, the balloon is deflated and thecrimp head is opened to allow the catheter to be removed. The scaffoldreceives a final alignment to the balloon markers. The scaffold andballoon are placed back into the crimp head. The operator initiatesstage 3 where the head is reduced to 0.070″ diameter for 10 seconds.During this stage 3, the balloon is also inflated to 17 psi. Oncecomplete, the machine moves automatically to the stage 4, where theballoon is deflated and the crimp head ID is reduced to 0.047″ and isheld for 200 seconds. When this fourth and final stage is complete, thehead opens and the catheter and scaffold removed. The scaffold isretained on the balloon and is immediately placed into a sheath, toprevent recoil of the scaffold.

The above study was conducted for PLLA. Similar results are contemplatedfor PLGA, if Tg for the different material is taken into considerationand assuming other characteristics of the process and scaffold pattern.For PLGA having % GA of about 5% the temperature ranges for crimping maybe between about 46 to 53 degrees Celsius. For PLGA having % GA of about15% the temperature ranges for crimping are about 43 to 50 degreesCelsius.

Based on the foregoing results, the following conclusions were reached.When the scaffold is crimped to a balloon while being heated totemperatures well within the range of Tg for the scaffold polymer, thereis a greater tendency for polymer chain re-alignment to occur that willresult in loss of strength when the scaffold is later deployed.Unacceptable crack formation (either in the number or extent of cracks),voids or outright fracture was observed in subsequent testing. It shouldbe noted that acceptable scaffolds have cracks. The degree of crackformation that cause a scaffold to be rejected is based on testsconducted on the scaffold when fully deployed, e.g., accelerated aging,fatigue, cyclic loading and static load tests and including a visualinspection of the scaffold.

It should be noted, therefore, that some degree of crack, or voidformation is permissible and indeed expected. Validation of a crimpingprocess, therefore, generally cannot be made by simply inspecting orcounting the number of cracks or voids. Testing is needed to establish,to a reasonable degree of confidence, a relationship between thelocations and nature of the imperfections at those locations in thescaffold and its ability to function properly. Mechanical testing isneeded to assess the degree of structural integrity in the deployedpolymer scaffolding. Then, relying on statistics a determination may bemade as to the type, number and/or location of cracks/voids thatdistinguish between an acceptable and unacceptable scaffold. A scaffold,despite the presence of one or more cracks and/or voids, may then bedeemed capable of being plastically expanded within a body lumen by theballoon to which it is crimped. As such, the scaffold is deemed capableof providing a therapeutic benefit to the body lumen including radiallysupporting the lumen despite the presence of one or more cracks/voids.

If the crimping temperature is raised too high relative to the Tg of thepolymer, the memory of the matrix material at the starting tubingdiameter is being removed, or reformed as the scaffold is deformed. As aconsequence, when the scaffold is later expanded under physiologicalconditions, e.g., body temperature, it becomes more susceptible to crackformation due to its brittle properties at body temperatures and lack ofchain alignment from its starting diameter. Retention force and scaffoldintegrity when crimped to the balloon generally improves at highertemperatures, however, the scaffold loses its structural integrity whenlater deployed if the temperature is raised too high relative to Tg. Onthe other hand, when the scaffold is heated to temperatures below about15 degrees Celsius of the glass transition temperature, or not heated atall, there is no noticeable improvement in scaffold retention. And ifthe crimping force is increased to improve scaffold retention at thesetemperatures, loss in strength occurs as cracks appear in the crimpedand deployed scaffold. It was concluded, therefore, that for atemperature below about 15 degrees from Tg the scaffold exhibited moreor less the same degree of fracture toughness it would exhibit underphysiological conditions.

Surprisingly, when the temperature range was raised to within a range ofabout 15 degrees below and up to about Tg there was a noticeable andconsistent improvement in scaffold retention force, without unacceptableloss in structural integrity for the deployed scaffold. It is believedthat when the polymer scaffold was crimped at a temperature slightlybelow its Tg (e.g., from 5 to 15 degrees Celsius below Tg), there arevery short chains of the matrix material that are able to freely move toassist in the deformation of the scaffold without exceeding materialstress limits. At the same time, the longer chains of the matrixsubstantially maintain their alignment, and, thus, stay intact withoutlosing their orientation set when the starting tube was expanded. Bydoing so, the scaffold may be crimped down to a diameter for goodscaffold retention, while the orientation of a majority of polymerchains would be the same to ensure desirable strength and fracturetoughness in the final product, i.e., when the stent is deployed tosupport a vessel.

The improved scaffold retention may also be explained in terms of theballoon-scaffold interaction. As noted above, when the temperature wasraised to within the range of Tg, there was improved scaffold retentionability. When the temperature was below about 15 degrees Celsius of Tgthere was no improvement (same crimping force used in both cases). Inthe former case, it is believed that with the increased temperaturethere is greater cohesion or contact between the scaffold and balloonresulting from the increased temperature. As the scaffold and balloonmaterial temperatures increase, the material becomes more compliantresulting in stronger adherence between the two surfaces, or greatersurface-to-surface contact. As a result, the retention force increases.For the tests, a PEBAX balloon was used.

While trends seen in the test data were in some ways hypothesized, itwas far from clear whether there existed a degree of polymer chainmovement induced within a temperature range that would make much, if anydifference in the outcome without also producing undesirable sideeffects. The stress-strain states of a polymer scaffold expanded to 2.5times its starting diameter (i.e., crimped to deployed) are difficult tounderstand through the empirical data, much less through analyticmodels. Moreover, the understanding in the art, as known to inventors,was that when a PLLA and PLGA scaffold is deformed, the effects oftemperature on scaffold properties, or stent scaffold retention would beminimal unless the temperature range fell within Tg. Notwithstandingthis common understanding, the inventors found that when the temperaturewas raised to, or near Tg, there was consistent improvement in thescaffold retention force for the polymer scaffold when crimped to theballoon, and without loss in structural integrity for the deployedscaffolding.

As noted above, in a preferred embodiment a stent scaffold has the stentpattern described in U.S. application Ser. No. 12/447,758 (U.S.2010/0004735) to Yang & Jow, et al. Other examples of stent patternssuitable for PLLA are found in U.S. 2008/0275537. FIG. 2 shows adetailed view of an intermediate portion 216 of a strut pattern 200depicted in U.S. 2010/0004735. The intermediate portion includes rings212 with linear ring struts 230 and curved hinge elements 232. The ringstruts 230 are connected to each other by hinge elements 232. The hingeelements 232 are adapted to flex, which allows the rings 212 to movefrom a non-deformed configuration to a deformed configuration. Line B-Blies on a reference plane perpendicular to the central axis 224 depictedin U.S. 2010/0004735. When the rings 212 are in the non-deformedconfiguration, each ring strut 230 is oriented at a non-zero angle Xrelative to the reference plane. The non-zero angle X is between 20degrees and 30 degrees, and more narrowly at or about 25 degrees. Also,the ring struts 230 are oriented at an interior angle Y relative to eachother prior to crimping. The interior angle Y is between 120 degrees and130 degrees, and more narrowly at or about 125 degrees. In combinationwith other factors such as radial expansion, having the interior anglebe at least 120 degrees results in high hoop strength when the stent isdeployed. Having the interior angle be less than 180 degrees allows thestent to be crimped while minimizing damage to the stent struts duringcrimping, and may also allow for expansion of the stent to a deployeddiameter that is greater than its initial diameter prior to crimping.Link struts 234 connect the rings 212. The link struts 234 are orientedparallel or substantially parallel to a bore axis of the stent. The ringstruts 230, hinge elements 232, and link struts 234 define a pluralityof W-shape closed cells 236. The boundary or perimeter of one W-shapeclosed cell 236 is darkened in FIG. 2 for clarity. In FIG. 2, theW-shapes appear rotated 90 degrees counterclockwise. Each of the W-shapeclosed cells 236 is immediately surrounded by six other W-shape closedcells 236, meaning that the perimeter of each W-shape closed cell 236merges with a portion of the perimeter of six other W-shape closed cells236. Each W-shape closed cell 236 abuts or touches six other W-shapeclosed cells 236.

Referring to FIG. 2, the perimeter of each W-shape closed cell 236includes eight of the ring struts 230, two of the link struts 234, andten of the hinge elements 232. Four of the eight ring struts form aproximal side of the cell perimeter and the other four ring struts forma distal side of the cell perimeter. The opposing ring struts on theproximal and distal sides are parallel or substantially parallel to eachother. Within each of the hinge elements 232 there is an intersectionpoint 238 toward which the ring struts 230 and link struts 234 converge.There is an intersection point 238 adjacent each end of the ring struts230 and link struts 234. Distances 240 between the intersection pointsadjacent the ends of rings struts 230 are the same or substantially thesame for each ring strut 230 of the strut pattern. The distances 242 arethe same or substantially the same for each link strut 234. The ringstruts 230 have widths 237 that are uniform in dimension along theindividual lengthwise axis 213 of the ring strut. The ring strut widths237 are between 0.15 mm and 0.18 mm, and more narrowly at or about 0.165mm. The link struts 234 have widths 239 that are also uniform indimension along the individual lengthwise axis 213 of the link strut.The link strut widths 239 are between 0.11 mm and 0.14 mm, and morenarrowly at or about 0.127 mm. The ring struts 230 and link struts 234have the same or substantially the same thickness in the radialdirection, which is between 0.10 mm and 0.18 mm, and more narrowly at orabout 0.152 mm.

As shown in FIG. 2, the interior space of each W-shape closed cell 236has an axial dimension 244 parallel to line A-A and a circumferentialdimension 246 parallel to line B-B. The axial dimension 244 is constantor substantially constant with respect to circumferential positionwithin each W-shape closed cell 236. That is, axial dimensions 244 Aadjacent the top and bottom ends of the cells 236 are the same orsubstantially the same as axial dimensions 244 B further away from theends. The axial and circumferential dimensions 244, 246 are the sameamong the W-shape closed cells 236.

It will be appreciated from FIG. 2 that the strut pattern for a stentthat comprises linear ring struts 230 and linear link struts 234 formedfrom a radially expanded and axially extended polymer tube. The ringstruts 230 define a plurality of rings 212 capable of moving from anon-deformed configuration to a deformed configuration. Each ring has acenter point, and at least two of the center points define the stentcentral axis. The link struts 234 are oriented parallel or substantiallyparallel to the stent central axis. The link struts 234 connect therings 212 together. The link struts 234 and the ring struts 230 definingW-shape closed cells 236. Each W-shaped cell 236 abuts other W-shapedcells. The ring struts 230 and hinge elements 232 on each ring 212define a series of crests and troughs that alternate with each other.Each crest on each ring 212 is connected by one of the link struts 234to another crest on an immediately adjacent ring, thereby forming anoffset “brick” arrangement of the W-shaped cells.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

What is claimed is:
 1. A method for crimping a balloon-expandable stentscaffolding to a balloon, comprising the steps of: providing a tubecomprising PLLA-(poly(L-lactide)) characterized by a glass transitiontemperature range having a lower limit of about 55° C.; radiallyexpanding the tube to increase its radial stiffness; forming thescaffolding from the radially-expanded tube including the steps offorming a circumferential series of closed cells having a W-shape andlinear link struts connecting the W-shape cells, the scaffolding havinga first diameter that is at least about 2.5 times greater than a finalcrimp diameter; and using a crimping device, crimping the scaffolding tothe balloon while the scaffolding has a temperature of between about 48°C. and 54° C., including the step of: crimping the scaffolding from thefirst diameter to a second diameter, removing the scaffolding from thecrimping device, returning the scaffolding to the crimping device,wherein the scaffolding is aligned on the balloon when the scaffoldingis returned to the crimping device, and crimping the scaffolding fromthe second diameter to the final crimp diameter.
 2. The method of claim1, wherein the crimping device includes jaws that apply a crimping forceon the scaffolding.
 3. The method of claim 1, wherein the balloon isfully inflated then the pressure released when crimping to the finalcrimp diameter.
 4. The method of claim 1, wherein the temperature isabout 48-50° C.
 5. The method of claim 4, wherein the scaffolding is onthe balloon when the scaffolding is being crimped from the firstdiameter to the second diameter.
 6. The method of claim 5, wherein thetemperature is about 48° C.
 7. The method of claim 1, wherein after thescaffolding diameter is decreased from the second diameter to the finalcrimp diameter the scaffolding has a retention force that is greaterthan 1.0 lbs and the scaffold has a length of 18 mm.
 8. The method ofclaim 1, wherein the crimping the scaffolding from the first diameter tothe second diameter includes reducing the scaffolding diameter from thefirst diameter to an intermediate diameter, followed by a first dwellperiod, then reducing the scaffolding diameter down from theintermediate diameter to the second diameter, followed by a second dwellperiod.
 9. A method for crimping a scaffolding, comprising the steps of:providing the scaffolding from a radially-expanded tube comprising apolymer characterized by a glass transition temperature (Tg), thescaffolding having a first diameter; positioning the scaffolding on aballoon having a diameter; increasing the pressure inside of the balloonso that the balloon diameter reaches the first diameter; and using acrimping device, crimping the scaffolding to the balloon while thescaffolding has a temperature of between about Tg-low and 15 degreesbelow Tg-low, including the steps of: crimping the scaffolding from thefirst diameter to a second diameter while the balloon is inflated,releasing the balloon pressure, and crimping the scaffolding from thesecond diameter to a final crimping diameter.
 10. The method of claim 9,wherein the final crimp diameter is about 2.5 times less than the firstdiameter.
 11. The method of claim 9, wherein the crimped scaffolding iscapable of being expanded to about 2.5 times the crimp diameter when theballoon is inflated.
 12. The method of claim 9, wherein the polymer ispoly(lactide-co-glycolide).
 13. The method of claim 9, wherein thecrimping device includes jaws that apply a crimping force on thescaffolding.
 14. The method of claim 9, wherein the balloon is fullyinflated then the pressure released when crimping to the final crimpdiameter.
 15. The method of claim 9, wherein after the scaffoldingdiameter is decreased from the second diameter to the final crimpdiameter the scaffolding has a retention force that is greater than 1.0lbs and the scaffold has a length of 18 mm.
 16. A method for crimping,comprising the steps of: providing a scaffolding comprising a polymercharacterized by a glass transition temperature (Tg), the scaffoldinghaving a first diameter that is at least about 2.5 times greater than afinal crimp diameter; using a crimping device, crimping the scaffoldingto a balloon while the scaffolding has a temperature of between aboutTg-low and 15 degrees below Tg-low, including the steps of: crimping thescaffolding from the first diameter to a second diameter, after crimpingto the second diameter and before crimping to the final crimp diameter,removing the scaffolding from the crimping device, returning thescaffolding to the crimping device, wherein the scaffolding is alignedon the balloon when the scaffolding is returned to the crimping device,and crimping the scaffolding from the second diameter to the final crimpdiameter.
 17. The method of claim 16, wherein the scaffolding receives afinal alignment on the balloon before crimping the scaffolding from thesecond diameter to the final crimp diameter.
 18. The method of claim 16,wherein the crimping device includes jaws that apply a crimping force onthe scaffolding.
 19. The method of claim 16, wherein the polymer ispoly(lactide-co-glycolide).
 20. The method of claim 19, wherein thecrimping temperature is between about 46 and 53 degrees Celsius.
 21. Themethod of claim 16, wherein the crimping the scaffolding from the firstdiameter to the second diameter includes reducing the scaffoldingdiameter from the first diameter to an intermediate diameter, followedby a first dwell period, then reducing the scaffolding diameter downfrom the intermediate diameter to the second diameter, followed by asecond dwell period.
 22. The method of claim 16, wherein the scaffoldingis formed from a tube comprising PLLA-(poly(L-lactide)).
 23. The methodof claim 22, wherein the tube is a radially-expanded tube.
 24. Themethod of claim 16, wherein the crimping step further includes inflatingthe balloon to support the balloon during crimping.
 25. The method ofclaim 16, wherein the scaffolding is aligned between balloon markerswhen the scaffolding is returned to the crimping device.
 26. The methodof claim 16, wherein the scaffolding is on the balloon when thescaffolding is being crimped from the first diameter to the seconddiameter.